Finding out why obesity leads to heart disease

Adipose tissue macrophage polarisation and Lipotoxicity

Obesity can lead to a number of serious or life-threatening diseases, including diabetes and heart disease. When adipose tissue cannot store any more fat, then the excess fats can go to other organs, poisoning them. This is called ‘lipotoxicity’, and can cause people to develop diabetes, or to become resistant to insulin, the hormone that controls how we use glucose. But fat in other organs is not always harmful – for example, athletes have more fat in certain organs but are not resistant to insulin. Scientists therefore think that it is not only the amount of fat that builds up that is harmful, but the type of fat itself. Fat tissue contains many different types of cell, one of which is an immune cell called a macrophage. Macrophages are important for allowing adipose tissue to get bigger and also to clear up dead cells. However, when people become too fat, the macrophages can produce harmful chemicals, which may influence the development of cardiovascular disease. Professor Antonio Vidal Puig at the University of Cambridge has found that macrophages at the early ‘healthier’ stages of obesity are different to those at later ‘unhealthy’ stages. Later stage macrophages produce more molecules that promote inflammation, contain different types of fats, and there are differences in their ‘fat-making’ genes. The BHF has now awarded a grant to Professor Vidal Puig to investigate how these different types of fat may affect how macrophages work, how changes in macrophages affect adipose tissue function in mice, and if the changes in macrophages are important in diabetes and heart disease.